Spinal cord injury occurs when axons or nerve fibers of the spinal cord are interrupted, generally by mechanical forces. If the spinal cord is compressed, severed or contused, the axons may be physically or physiologically disintegrated, so that no conduction of neuroelectric impulses can occur along the affected axon's length. Eventually, large populations of axons and their associated cell bodies may die, causing massive loss in communication between the brain and the peripheral nerves, resulting in varying degrees of functional deficit. Currently available therapies have demonstrated only limited success in restoring function following spinal cord injury.
The fibrous scar that develops after spinal cord injury is considered a major impediment for axonal regeneration. Spinal cord scarring generally means the recruitment and proliferation of glial cells to the site of injury. The densely packed cells (primarily reactive astrocytes) and their secretions form a dense cellular plaque known as the glial scar. This scar prevents axons from projecting through. In response to injury to the central nervous system (CNS), reactive astrocytes appear and accumulate in the wounded area, leading to glial scar formation. Glial scar is the physical barrier to axonal regeneration of injured neurons. Chondroitin sulfate proteoglycans are inhibitory to axon outgrowth and are upregulated in reactive astrocytes upon CNS injury. It is known that keratin sulfate proteoglycans (KSPGs) are also augmented after CNS injury and act as inhibitory cues.
Therapeutic treatments aimed at suppression of fibrous scarring have been shown to promote axon regeneration in various lesion paradigms of the mammalian spinal cord.
To date, no treatment option exists that is able to promote healing, reduce fibrous scarring, ameliorate cellular damage following spinal cord injury, provide neuroprotection or induce the growth and development of spinal cord cells to replace damaged or dead cells, any or all of which could help return the injured patient to normal or near normal function. Therefore, it is an object of the instant invention to provide such treatment options for spinal cord injury patients.